lipl-4 Research Notes

Gene Overview

lipl-4 (K04A8.5) encodes a lysosomal acid lipase in C. elegans with sequence and functional similarity to human LIPA (lysosomal acid lipase). It is a key enzyme in the lysosome-to-nucleus retrograde lipid signaling pathway that promotes longevity.

Core Pathway: LIPL-4 → LBP-8 → NHR-49/NHR-80

The central discovery is that LIPL-4 generates lipid signaling molecules in the lysosome, which are then transported to the nucleus by the lipid chaperone LBP-8 to activate transcription factors NHR-49 and NHR-80 PMID:25554789.

Key lipid signals produced by LIPL-4:

  1. Oleoylethanolamide (OEA) - an N-acylethanolamine fatty acid derivative. OEA directly binds LBP-8 (with ~3x higher affinity than fatty acids) and NHR-80 (Kd ~7.8 µM). OEA supplementation extends lifespan PMID:25554789.
  2. Omega-6 PUFAs (AA, DGLA) - these activate autophagy, extending lifespan PMID:23392608.

Enzymatic Activity

Subcellular Localization

Longevity Function

Autophagy Connection

Regulation

Downstream Signaling